Diagnosis of CF despite normal or borderline sweat chloride

Abstract

Research over the last 20 years has identified the CF gene and its product, the cystic fibrosis transmembrane regulator (CFTR), has defined the physiologic functions of CFTR as a chloride channel and regulator of other channels including the sodium channel, and has identified numerous CFTR gene mutations in patients with cystic fibrosis. In addition, this research has provided additional diagnostic tests, including CFTR gene mutation analysis and evaluation of CFTR function using nasal potential difference testing. While these diagnostic tests have expanded our ability to diagnose cystic fibrosis in patients with borderline sweat chloride values, inappropriate use and/or interpretation of these studies can lead to the incorrect conclusion that a particular patient does (or does not) have cystic fibrosis. The results of these studies must be considered with other clinical information and diagnostic studies to determine if a patient fulfills the diagnostic criteria for cystic fibrosis. Advances in our understanding of the spectrum of CFTR gene mutations and CFTR physiologic function have changed our approach to diagnosing cystic fibrosis. In the past, the presence of clinical features of cystic fibrosis or a family history prompted sweat chloride testing; and, the diagnosis of cystic fibrosis was made if two or more sweat chloride determinations were elevated (greater than 60mmol/L). Rarely, a patient with prominent clinical features of cystic fibrosis but borderline or normal sweat chloride values was identified and may have been labelled as “CF variant”. Extensive evaluations of several patients with clinical features of CF